U. team touts gene 'linkage'

A technique that uses families to identify chromosomes that have certain genes may help unravel the mystery of major depressive disorder, which affects as many as 17 percent of Americans.

University of Utah School of Medicine researchers, in an article just published in the journal Trends in Molecular Medicine, looked at seven different studies (including one by the U.) to show that the technique called linkage analysis may have more to say about what causes major depressive disorder (MDD) than was previously thought.

Major strides using the technique have been made in other mental illnesses, including bipolar disorder and schizophrenia, said Nicola J. Camp, associate professor of medical informatics and the study's lead author. But "nobody thought it was worth looking at using linkage analysis with (MDD) because it is so common" and the technique has proven so complex with other mental illnesses.

But research into specific areas of MDD, including people who have recurrent episodes or early onset depression, even the higher incidence in women, indicates there may be value in linkage analysis for MDD.

MDD is the leading cause of disability among people age 15-44. Its estimated annual cost is as much as $43 billion.

The seven studies reviewed showed something "surprising but it bodes quite well for the future," Camp said. "Researchers have noted several areas where such genes might be seen, areas that overlap with some other types of mental illness.

"We may be able to use linkage analysis to find the chromosomes that might have genes that predispose people, then hopefully we can move from linkage analysis to use of positional cloning techniques . . . to actually home in on an actual gene and see the variants."

That means that recurring and early onset major depressions are perhaps more genetically based than had been thought, she said.

"We know life events can predispose anyone. Environmental factors are huge."

The finding has led Camp to believe that "perhaps if we take more notice of what other psychiatric disorders are in the family," researchers can find genes that could be targeted for new therapies.

If there is a genetic link, she said, Utah is a logical place to study it. The state has distinguished itself in familial medical research because of different databases that contain information about large families.

When predisposition genes are passed from parent to child, the genetic markers near the gene tend to stay with the gene, passed from one generation to the next. By studying families in which the depression is passed, researchers can find which genetic markers are shared and find that genes that cause a disease are on the chromosomes near the markers.

Camp looked at seven recent genomewide linkage studies of families in which MDD occurred, identifying six chromosomes that would be good places to look for MDD predisposition genes.

The study was co-authored by Lisa A. Cannon-Albright, U. professor of medical informatics.

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